This is a revised application for renewal of the SPORE in Prostate Cancer at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Cancer Research Center of the University of Chicago. Overall, the reviewers noted that the Program had considerable merit with strengths in the expertise of the investigators, large patient population and an environment highly supportive of the SPORE. We have responded to the comments made by the review committee through extensive revisions and, thus, have further enhanced the program throughout. The major changes can be found in Project 4 where we now focus on animal studies and a clinical trial and in Project 2 where we have eliminated one aim to conduct animal studies. The revised application contains four highly translational research projects: (1) 5a-Reductase Inhibition in Intermittent Androgen Ablation Therapy of Prostate Cancer (Wang & Shevrin), (2) PEDF Regulation of Adipogenesis and Leptin in Prostate Cancer (Crawford, Gapstur and Lee), (3) Radiation-lnducible TNF-alpha Therapy in Prostate Cancer (Weichselbaum & Stadler) and (4) Modulation of Prostate Cancer Cell Motility by the Chemopreventive Agent Genistein (Bergan & Catalona). These projects represent a balanced approach in prostate cancer translational research, including prevention (Project 4), molecular epidemiology (Project 2), management of androgen-sensitive advanced cancer (Project 1), and therapy of local disease (project 3). The leadership of the SPORE emphasizes the highly interactive structures in place for the proposed four cores, that include the Administrative Core, the Specimen Procurement Core, the Biostatistics/Bioinformatics Core, and the Clinical Trials and Advocacy Core. The SPORE also has flexible, yet structured, Developmental Research and Career Development Programs to encourage additional investigators to undertake initiatives in prostate cancer research and to quickly respond to new research opportunities. The Internal and External Advisory Committees evaluate program progress and offer guidance to the SPORE principal investigator and co-principal investigators. We feel that the revised application is significantly improved, and we are grateful to the reviewers for their helpful comments.